Related Experiment Video

Updated: Jul 24, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma

Kaja Kostyrko1, Marta Román2, Alex G Lee2

  • 1Division of Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA. kaja.kostyrko@ucsf.edu.

Nature Communications
|July 5, 2023
PubMed

Insights

Researchers identified Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as a vulnerability in KRAS-mutant lung cancer. Targeting UHRF1 may offer a new therapeutic strategy for these specific lung cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • KRAS mutations are common drivers in lung cancer, presenting a need for targeted therapies.
  • Identifying KRAS-specific vulnerabilities is crucial for developing effective lung cancer treatments.

Purpose of the Study:

  • To discover KRAS-specific vulnerabilities in lung cancer.
  • To investigate the role of the epigenetic regulator UHRF1 in KRAS-driven lung cancer.

Main Methods:

  • RNAi screens in primary mouse lung cancer spheroids.
  • UHRF1 knockout in human lung cancer models.
  • Genome-wide methylation and gene expression analysis.
  • CRISPR/Cas9 screening and in vivo tumor growth studies.

Main Results:

  • UHRF1 knockout selectively impaired growth and induced apoptosis in KRAS-mutant lung cancer cells.
  • UHRF1 depletion led to global DNA hypomethylation and upregulation of tumor suppressor genes (TSGs).
  • In vivo, UHRF1 knockout inhibited tumor growth in KRAS-driven lung cancer models.
  • High UHRF1 expression in patients correlated with decreased TSG expression and worse outcomes in KRAS-mutant lung cancer.

Conclusions:

  • UHRF1 is a KRAS-specific vulnerability in lung cancer.
  • UHRF1 represents a potential therapeutic target for KRAS-mutant lung cancer.

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